Available evidence indicates that the coagulation system contributes to tissue damage in a variety of immunologic disease states, but mechanisms triggering the coagulation sequence in these disease states are poorly understood. We recently shown that antigen-antibody complexes and allogenic stimulation markedly increase production and expression of tissue thromboplastin-like activity by human leukocytes in vitro, and this activity is a potent initiator of the blood clotting pathway. We now propose to examine the possibility that similar activity is produced by leukocytes in immunologic inflammatory reactions characterized by thrombosis and presence of antigen-antibody complexes and/or allogenic stimulation. The immunologic disorders to be studied will include hyperacute, acute, and chronic renal allograft rejection and autoimmune hemolysis. Leukocytes will be isolated from the blood and tissues of human subjects and animal models with defined stages of disease, and the procoagulant activity of these cells will be assayed using one-stage clotting tests. In vitro reactions will be utilized in order to investigate possible mechanisms of stimulating procoagulant activity production by leukocytes with autoantibodies and antibodies directed against histocompatibility antigens. The overall goal is to clarify the role of leukocyte as an initiator of thrombosis in immunologic inflammatory reactions.